Gene: RPE65

Alternate names for this Gene: BCO3|LCA2|RP20|mRPE65|p63|rd12|sRPE65

Gene Summary: The protein encoded by this gene is a component of the vitamin A visual cycle of the retina which supplies the 11-cis retinal chromophore of the photoreceptors opsin visual pigments. It is a member of the carotenoid cleavage oxygenase superfamily. All members of this superfamily are non-heme iron oxygenases with a seven-bladed propeller fold and oxidatively cleave carotenoid carbon:carbon double bonds. However, the protein encoded by this gene has acquired a divergent function that involves the concerted O-alkyl ester cleavage of its all-trans retinyl ester substrate and all-trans to 11-cis double bond isomerization of the retinyl moiety. As such, it performs the essential enzymatic isomerization step in the synthesis of 11-cis retinal. Mutations in this gene are associated with early-onset severe blinding disorders such as Leber congenital.

Gene is located in Chromosome: 1

Location in Chromosome : 1p31.3

Description of this Gene: retinoid isomerohydrolase RPE65

Type of Gene: protein-coding

rs988133284 in RPE65 gene and ACTH Deficiency, Isolated PMID 30576320 2018 Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis.

rs121917744 in RPE65 gene and LEBER CONGENITAL AMAUROSIS, TYPE II (disorder) PMID 11462243 2001 Four novel mutations in the RPE65 gene in patients with Leber congenital amaurosis.

PMID 10090910 1999 Different functional outcome of RetGC1 and RPE65 gene mutations in Leber congenital amaurosis.

PMID 14962443 2004 Thirty-year follow-up of a patient with leber congenital amaurosis and novel RPE65 mutations.

PMID 14611946 2003 Analysis of three genes in Leber congenital amaurosis in Indonesian patients.

PMID 10766140 2000 Mutation analysis of 3 genes in patients with Leber congenital amaurosis.

PMID 9801879 1999 Autosomal recessive retinal dystrophy associated with two novel mutations in the RPE65 gene.

PMID 15024725 2004 Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis.

PMID 16205573 2005 Evaluation of genotype-phenotype associations in leber congenital amaurosis.

PMID 17724218 2007 Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients.

PMID 9326927 1997 Mutations in RPE65 cause Leber's congenital amaurosis.

PMID 9326941 1997 Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy.

PMID 17297704 2006 Gene symbol: RPE65. Disease: Leber's congenital amaurosis. Accession #Hm0548.

PMID 16828753 2006 Impacts of two point mutations of RPE65 from Leber's congenital amaurosis on the stability, subcellular localization and isomerohydrolase activity of RPE65.

PMID 28418496 2017 Homozygosity Mapping and Genetic Analysis of Autosomal Recessive Retinal Dystrophies in 144 Consanguineous Pakistani Families.

PMID 18682808 2008 Molecular characterization of Leber congenital amaurosis in Koreans.

PMID 15557452 2004 A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers.

PMID 29681726 2018 Early onset flecked retinal dystrophy associated with new compound heterozygous RPE65 variants.

PMID 26626312 2016 Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark.

PMID 26906952 2016 Preserved visual function in retinal dystrophy due to hypomorphic RPE65 mutations.

PMID 25752820 2015 Temperature-sensitive retinoid isomerase activity of RPE65 mutants associated with Leber Congenital Amaurosis.

PMID 25495949 2016 RPE65 Mutations in Two Japanese Families with Leber Congenital Amaurosis.

PMID 19959640 2010 Differential macular morphology in patients with RPE65-, CEP290-, GUCY2D-, and AIPL1-related Leber congenital amaurosis.

PMID 26024124 2015 Autofluorescence imaging with near-infrared excitation:normalization by reflectance to reduce signal from choroidal fluorophores.

PMID 20604683 2010 Molecular anthropology meets genetic medicine to treat blindness in the North African Jewish population: human gene therapy initiated in Israel.

PMID 21151602 2010 Mutation analysis of 272 Spanish families affected by autosomal recessive retinitis pigmentosa using a genotyping microarray.

PMID 21911650 2012 Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years.

PMID 16150724 2005 Mutation of key residues of RPE65 abolishes its enzymatic role as isomerohydrolase in the visual cycle.

PMID 18539930 2008 Photoreceptor layer topography in children with leber congenital amaurosis caused by RPE65 mutations.

PMID 20079931 2010 Visual acuity in patients with Leber's congenital amaurosis and early childhood-onset retinitis pigmentosa.

PMID 19431183 2009 Predicting the pathogenicity of RPE65 mutations.

PMID 21153841 2011 Potential involvement of more than one locus in trait manifestation for individuals with Leber congenital amaurosis.

PMID 16754667 2006 Two point mutations of RPE65 from patients with retinal dystrophies decrease the stability of RPE65 protein and abolish its isomerohydrolase activity.

PMID 11095629 2000 Genetics and phenotypes of RPE65 mutations in inherited retinal degeneration.

PMID 19117922 2009 Defining the residual vision in leber congenital amaurosis caused by RPE65 mutations.

PMID 9501220 1998 Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis.

PMID 19854499 2009 Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial.

PMID 20683928 2010 Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes.

PMID 16096063 2005 Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium.

PMID 26427455 2016 Functional Rescue of Retinal Degeneration-Associated Mutant RPE65 Proteins.

PMID 28181551 2017 Whole exome sequencing using Ion Proton system enables reliable genetic diagnosis of inherited retinal dystrophies.

rs199683808 in RPE65 gene and Retinal Dystrophies PMID 18599565 2008 A comprehensive clinical and biochemical functional study of a novel RPE65 hypomorphic mutation.

PMID 9326941 1997 Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy.

rs368088025 in RPE65 gene and Retinitis Pigmentosa PMID 30718709 2019 Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.

rs121917744 in RPE65 gene and Retinitis Pigmentosa 20 PMID 16828753 2006 Impacts of two point mutations of RPE65 from Leber's congenital amaurosis on the stability, subcellular localization and isomerohydrolase activity of RPE65.

PMID 11095629 2000 Genetics and phenotypes of RPE65 mutations in inherited retinal degeneration.

PMID 26626312 2016 Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark.

PMID 9501220 1998 Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis.

PMID 29681726 2018 Early onset flecked retinal dystrophy associated with new compound heterozygous RPE65 variants.

PMID 15557452 2004 A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers.

PMID 12960219 2003 A Tyr368His RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population.

PMID 25752820 2015 Temperature-sensitive retinoid isomerase activity of RPE65 mutants associated with Leber Congenital Amaurosis.

PMID 23878505 2013 Novel mutations in RPE65 identified in consanguineous Pakistani families with retinal dystrophy.

PMID 26906952 2016 Preserved visual function in retinal dystrophy due to hypomorphic RPE65 mutations.

PMID 25495949 2016 RPE65 Mutations in Two Japanese Families with Leber Congenital Amaurosis.

PMID 22334370 2012 Next-generation genetic testing for retinitis pigmentosa.

PMID 19959640 2010 Differential macular morphology in patients with RPE65-, CEP290-, GUCY2D-, and AIPL1-related Leber congenital amaurosis.

PMID 21911650 2012 Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years.

PMID 20604683 2010 Molecular anthropology meets genetic medicine to treat blindness in the North African Jewish population: human gene therapy initiated in Israel.

PMID 26024124 2015 Autofluorescence imaging with near-infrared excitation:normalization by reflectance to reduce signal from choroidal fluorophores.

PMID 15024725 2004 Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis.

PMID 17724218 2007 Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients.

PMID 21151602 2010 Mutation analysis of 272 Spanish families affected by autosomal recessive retinitis pigmentosa using a genotyping microarray.

PMID 16150724 2005 Mutation of key residues of RPE65 abolishes its enzymatic role as isomerohydrolase in the visual cycle.

PMID 20079931 2010 Visual acuity in patients with Leber's congenital amaurosis and early childhood-onset retinitis pigmentosa.

PMID 18539930 2008 Photoreceptor layer topography in children with leber congenital amaurosis caused by RPE65 mutations.

PMID 11462243 2001 Four novel mutations in the RPE65 gene in patients with Leber congenital amaurosis.

PMID 19431183 2009 Predicting the pathogenicity of RPE65 mutations.

PMID 18682808 2008 Molecular characterization of Leber congenital amaurosis in Koreans.

PMID 16754667 2006 Two point mutations of RPE65 from patients with retinal dystrophies decrease the stability of RPE65 protein and abolish its isomerohydrolase activity.

PMID 19117922 2009 Defining the residual vision in leber congenital amaurosis caused by RPE65 mutations.

PMID 21153841 2011 Potential involvement of more than one locus in trait manifestation for individuals with Leber congenital amaurosis.

PMID 20683928 2010 Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes.

PMID 19854499 2009 Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial.

PMID 26427455 2016 Functional Rescue of Retinal Degeneration-Associated Mutant RPE65 Proteins.

PMID 16096063 2005 Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium.

PMID 28181551 2017 Whole exome sequencing using Ion Proton system enables reliable genetic diagnosis of inherited retinal dystrophies.

PMID 10766140 2000 Mutation analysis of 3 genes in patients with Leber congenital amaurosis.